Ventilatory Efficiency in Transgender Women: Implications of Gender-Affirming Hormone Therapy on Cardiorespiratory Responses

Abstract

Background Ventilatory efficiency, a key parameter of cardiopulmonary function assessed through cardiopulmonary exercise testing (CPET), often demonstrates significant variability in transgender women due to the physiological changes induced by gender-affirming hormone therapy. Understanding these differences is essential for optimizing clinical management and enhancing health outcomes within this population. Research Question How do ventilatory efficiency, particularly the carbon dioxide ventilatory equivalent (VE/VCO2), and other CPET variables differ between transgender women and matched cisgender controls, offering insights into the physiological impacts of gender-affirming hormone therapy? Study Design and Methods This case-control study included 51 participants, comprising 17 transgender women matched 1:1:1 by age, body mass index, and physical activity levels with cisgender women and cisgender men. CPET assessments were conducted between August 2018 and September 2019, before the COVID-19 pandemic. Results Transgender women demonstrated significantly higher VE/VCO2 ratios at rest (31.4 ± 2.9), at the first ventilatory threshold (34.9 ± 3.9), and peak exercise (39.3 ± 5.3) compared to cisgender women (28.2 ± 2.5; 31.8 ± 3.2; 35.4 ± 4.4, respectively) and cisgender men (27.4 ± 2.1; 30.8 ± 2.6; 34.3 ± 3.5, respectively), with all comparisons reaching statistical significance (p < 0.001) and large effect sizes (η2 = 0.30–0.34). The VE/VCO2 slope was also significantly elevated in transgender women (33.9 ± 4.2) compared to cisgender women (29.5 ± 5.0) and cisgender men (28.0 ± 3.5) (p < 0.001; η2 = 0.29), indicating reduced ventilatory efficiency across the effort continuum. Interpretation This study highlights substantial ventilatory inefficiencies in transgender women, likely associated with gender-affirming hormone therapy, underscoring the need for tailored clinical strategies to address these cardiopulmonary adaptations. These findings provide critical insights into the unique health needs of transgender individuals, contributing valuable data to support evidence-based care.